TFA-Mediated Synthesis of 1,2,4-Oxadiazoles from Carbamates and Nitriles.

An unprecedented protocol for the synthesis of 1,2,4-oxadiazoles from carbamates has been developed by employing nitriles as both substrates and solvents. This one-pot procedure achieves the formation of C═N bonds via TFA-mediated [3+2] annulation. A series of 1,2,4-oxadiazoles are synthesized in moderate to good yields.

Synthesis of isothiocyanato alkyl sulfides from alkenes using KSCN and DMTSM.

A method for the synthesis of isothiocyanato alkyl sulfides from KSCN and DMTSM under metal-free conditions has been developed. The features of this reaction are low-cost, readily accessible starting materials and the use of KSCN as nucleophiles for C-NCS bond formation. Alkenes with various substituted groups react smoothly and the desired products are obtained in moderate to good yields.

The expression profiles of cyp19a1, sf-1, esrs and gths in the brain-pituitary during gonadal sex differentiation in juvenile Japanese eels.

Eels are gonochoristic species whose gonadal differentiation initiates at the yellow eel stage and is influenced by environmental factors. We revealed some sex-related genes were sex dimorphically expressed in gonads during gonadal sex differentiation of Japanese eel (Anguilla japonica); however, the expression of sex-related genes in the brain-pituitary during gonadal sex differentiation in eels is still unclear. This study aimed to investigate the sex-related gene expressions in the brain-pituitary and tried to clarify their roles in the brain and gonads during gonadal sex differentiation. Based on our previous histological study, the control eels developed as males, and estradiol-17ß (E2) was used for feminization. Our results showed that during testicular differentiation, the brain cyp19a1 transcripts and aromatase proteins were increased significantly; moreover, the cyp19a1, sf-1, foxl2s, and esrs (except gperb) transcripts in the midbrain/pituitary also were increased significantly. Forebrain gnrh1 transcripts increased slightly during gonadal differentiation of both sexes, but the gnrhr1b and gnrhr2 transcripts in the midbrain/pituitary were stable during gonadal differentiation. The expression levels of gths and gh in the midbrain/pituitary were significantly increased during testicular differentiation and were much higher in males than in E2-feminized females. These results implied that endogenous estrogens might play essential roles in the brain/pituitary during testicular differentiation, sf-1, foxl2s, and esrs may have roles in cyp19a1 regulation in the midbrain/pituitary of Japanese eels. For the GnRH-GTH axis, gths, especially fshb, may be regulated by esrs and involved in regulating testicular differentiation and development in Japanese eels.

ATXN3 promotes prostate cancer progression by stabilizing YAP.

BACKGROUND: Prostate cancer (PC) is the most common neoplasm and is the second leading cause of cancer-related deaths in men worldwide. The Hippo tumor suppressor pathway is highly conserved in mammals and plays an important role in carcinogenesis. YAP is one of major key effectors of the Hippo pathway. However, the mechanism supporting abnormal YAP expression in PC remains to be characterized. METHODS: Western blot was used to measure the protein expression of ATXN3 and YAP, while the YAP target genes were measured by real-time PCR. CCK8 assay was used to detect cell viability; transwell invasion assay was used to measure the invasion ability of PC. The xeno-graft tumor model was used for in vivo study. Protein stability assay was used to detect YAP protein degradation. Immuno-precipitation assay was used to detect the interaction domain between YAP and ATXN3. The ubiquitin-based Immuno-precipitation assays were used to detect the specific ubiquitination manner happened on YAP. RESULTS: In the present study, we identified ATXN3, a DUB enzyme in the ubiquitin-specific proteases family, as a bona fide deubiquitylase of YAP in PC. ATXN3 was shown to interact with, deubiquitylate, and stabilize YAP in a deubiquitylation activity-dependent manner. Depletion of ATXN3 decreased the YAP protein level and the expression of YAP/TEAD target genes in PC, including CTGF, ANKRD1 and CYR61. Further mechanistic study revealed that the Josephin domain of ATXN3 interacted with the WW domain of YAP. ATXN3 stabilized YAP protein via inhibiting K48-specific poly-ubiquitination process on YAP protein. In addition, ATXN3 depletion significantly decreased PC cell proliferation, invasion and stem-like properties. The effects induced by ATXN3 depletion could be rescued by further YAP overexpression. CONCLUSIONS: In general, our findings establish a previously undocumented catalytic role for ATXN3 as a deubiquitinating enzyme of YAP and provides a possible target for the therapy of PC. Video Abstract.

All-trans retinoic acid impairs glucose-stimulated insulin secretion by activating the RXR/SREBP-1c/UCP2 pathway.

Diabetes is often associated with vitamin A disorders. All-trans retinoic acid (ATRA) is the main active constituent of vitamin A. We aimed to investigate whether ATRA influences diabetic progression and its mechanisms using both Goto-Kazizazi (GK) rats and INS-1 cells. Rat experiments demonstrated that ATRA treatment worsened diabetes symptoms, as evidenced by an increase in fasting blood glucose (FBG) levels and impairment of glucose homeostasis. Importantly, ATRA impaired glucose-stimulated insulin secretion (GSIS) and increased the expression of sterol regulatory element-binding protein 1c (SREBP-1c) and uncoupling protein 2 (UCP2) in the rat pancreas. Data from INS-1 cells also showed that ATRA upregulated SREBP-1c and UCP2 expression and impaired GSIS at 23 mM glucose. Srebp-1c or Ucp2 silencing attenuated GSIS impairment by reversing the ATRA-induced increase in UCP2 expression and decrease in ATP content. ATRA and the retinoid X receptor (RXR) agonists 9-cis RA and LG100268 induced the gene expression of Srebp-1c, which was almost completely abolished by the RXR antagonist HX531. RXRα-LBD luciferase reporter plasmid experiments also demonstrated that ATRA concentration-dependently activated RXRα, the EC50 of which was 1.37 µM, which was lower than the ATRA concentration in the pancreas of GK rats treated with a high dose of ATRA (approximately 3 µM), inferring that ATRA can upregulate Srebp-1c expression in the pancreas by activating RXR. In conclusion, ATRA impaired GSIS partly by activating the RXR/SREBP-1c/UCP2 pathway, thus worsening diabetic symptoms. The results highlight the roles of ATRA in diabetic progression and establish new strategies for diabetes treatment.

Workers' compensation prescription medication patterns and associated outcomes.

BACKGROUND: Opioid use in the treatment of musculoskeletal injuries is a complex decision where benefits must be balanced with risk. Previous research has shown an association between higher opioid doses and adverse health effects. The study's objective was to investigate whether opioid prescriptions are associated with increased costs and deaths through an injury mechanism or as a direct result of the opioid prescription. METHODS: Data for 144,553 deidentified Ohio Bureau of Workers' Compensation claims from 2010 to 2014 with shoulder, knee, and low back injuries were obtained and followed until 2016. Each claim had associated prescription information. Injury claims were further classified using the allowed diagnoses by single or multiple body areas affected and injury severity ("simple" or "complex"). The outcome variables were medical and indemnity costs, lost days, MaxMED (maximum claim-prescribed daily morphine equivalent dose), and death status. Association between maximum opioid dose with deaths was determined by logistic regression analysis. RESULTS: Several outcome variables, including claim medical and indemnity costs, and the likelihood of claimant death, showed significant associations with the MaxMED. In the analysis of claim deaths, these associations held for all claim types (except complex), even after adjusting for age, gender, surgery, and lost time. CONCLUSION: The association between increasing opioid doses and deaths for low-severity diagnoses was disturbing given the lack of demonstrated efficacy of opioids for treatment of minor injuries. A focus on provider education, increased utilization of non-opioids, and early intervention for minor soft-tissue injuries could reduce claims costs, disability, and future deaths.

SOX5 promotes cell growth and migration through modulating the DNMT1/p21 pathway in bladder cancer.

Bladder cancer (BC) is one of the most prevalent and life-threatening cancers among the male population worldwide. Sex determining region Y-box protein 5 (SOX5) plays important roles in a variety of human cancers. However, little research has been conducted on the function and underlying mechanism of SOX5 in BC. In the present study, we first reveal the increased expression of SOX5 in BC tissues and in vitro cells lines. Second, we discover that inhibition of SOX5 inhibits cell growth and migration but promotes cell apoptosis. Meanwhile, ectopic SOX5 expression stimulates cell growth and migration in BC cells. Then, we show that suppressing SOX5 inhibits the expression of DNA methyltransferase 1 (DNMT1), and that overexpressing DNMT1 alleviates the cell progress of BC cells inhibited by SOX5. Furthermore, we demonstrate that DNMT1 inhibits p21 expression by affecting DNA methylation of the p21 promoter. Collectively, we demonstrate that SOX5 exerts its functions in BC cells by modulating the SOX5/DNMT1/p21 pathway. Finally, we demonstrate that SOX5 knockdown inhibits xenograft tumor growth in vivo. In conclusion, our study elucidates the oncogenic role of SOX5 and its underlying molecular mechanism in BC, and reveals a novel pathway which has the potential to serve as a diagnostic biomarker and therapeutic target for BC.

Short-chain fatty acids exert opposite effects on the expression and function of p-glycoprotein and breast cancer resistance protein in rat intestine.

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are involved in intestinal barrier. Short-chain fatty acids (SCFAs) play important roles in maintaining intestinal barrier. In this study we explored how SCFAs affected the expression and function of intestinal P-gp and BCRP in rats. Rats received 150 mM acetate, propionate or butyrate in drinking water for 4 weeks. In SCFA-treated rats, the expression and function of intestinal P-gp were decreased, but those of intestinal BCRP were increased; intestinal p-p65 was also decreased, which was positively related to P-gp protein expression. Among the three SCFAs tested, butyrate exhibited the strongest induction or inhibitory effect, followed by propionate and acetate. Similar results were observed in mouse primary enterocytes and Caco-2 cells treated with acetate (5 mM), propionate (2 mM), or butyrate (1 mM). In Caco-2 cells, addition of butyrate, vorinostat, and valproate (two classic HDAC inhibitors), Bay117082 (selective inhibitor of NF-κB activation) or NF-κB p65 silencing significantly decreased the expression of P-gp and the level of phosphorylated p65 (p-p65). Furthermore, butyrate attenuated the expression of P-gp and p-p65 induced by TNF-α (NF-κB activator) and theophylline (HDAC activator). However, vorinostat, valproate, Bay117082, TNF-α or p65 silencing hardly affected BCRP protein expression. But GW9662 (selective PPARγ antagonist) or PPARγ silencing abolished BCRP induction by butyrate and troglitazone (PPARγ agonist). SCFAs-treated rats showed higher intestinal protein expression of PPARγ, which was positively related to BCRP protein expression. Butyrate increased plasma exposure of fexofenadine but decreased that of rosuvastatin following oral dose to rats. In conclusion, SCFAs exert opposite effects on the expression and function of intestinal P-gp and BCRP; butyrate downregulated P-gp expression and function possibly via inhibiting HDAC/NF-κB pathways; butyrate induced BCRP expression and function partly via PPARγ activation.

Extensive Scarring Alopecia Treated Through a Single Dense-Packing Follicular Unit Extraction Megasession.

BACKGROUND: Follicular unit extraction (FUE) is becoming more popular in hair restoration. However, its potential for treating extensive scarring alopecia is unknown. METHODS: Patients with scarring alopecia larger than 100 cm2 were enrolled from 2015 to 2018. After assessing scar quality regarding vascularity, pliability, and thickness, dense-packing megasession (DPM)-FUE was performed on high-quality recipient sites. Patients were followed up at 1 week and 12 months postoperatively to evaluate complications, survival rates of grafts, and patient satisfactions. Cases of nonscarring alopecia were reviewed as controls. RESULTS: Fifty-two scarring alopecia and 55 nonscarring alopecia patients were enrolled. The mean scar area was 120 cm2, and the procedure required an average of 8 operative hours, with no difference between groups (p > .05). Graft amount and postoperative complications were similar as well (p > .05). The survival rate in scarring alopecia was lower than that in the control but was still 85% (p < .05). Follow-up photographs showed effective scar camouflage after DPM-FUE. Most patients were very satisfied with the final results (p > .05). CONCLUSION: DPM-FUE is a safe and effective treatment for extensive scarring alopecia.

Diabetes downregulates peptide transporter 1 in the rat jejunum: possible involvement of cholate-induced FXR activation.

Peptide transporter 1 (PepT1), highly expressed on the apical membrane of enterocytes, is involved in energy balance and mediates intestinal absorption of peptidomimetic drugs. In this study, we investigated whether and how diabetes affected the function and expression of intestinal PepT1. Diabetes was induced in rats by combination of high-fat diet and low dose streptozocin injection. Pharmacokinetics study demonstrated that diabetes significantly decreased plasma exposures of cephalexin and acyclovir following oral administration of cephalexin and valacyclovir, respectively. Single-pass intestinal perfusion analysis showed that diabetes remarkably decreased cephalexin absorption, which was associated with decreased expression of intestinal PepT1 protein. We assessed the levels of bile acids in intestine of diabetic rats, and found that diabetic rats exhibited significantly higher levels of chenodeoxycholic acid (CDCA), cholic acid (CA) and glycocholic acid (GCA), and lower levels of lithocholic acid (LCA) and hyodeoxycholic acid (HDCA) than control rats; intestinal deoxycholic acid (DCA) levels were unaltered. In Caco-2 cells, the 6 bile acids remarkably decreased expression of PepT1 protein with CDCA causing the strongest inhibition, whereas TNF-α, LPS and insulin little affected expression of PepT1 protein; short-chain fatty acids induced rather than decreased expression of PepT1 protein. Farnesoid X receptor (FXR) inhibitor glycine-ß-muricholic acid or FXR knockdown reversed the downregulation of PepT1 expression by CDCA and GW4064 (another FXR agonist). In diabetic rats, the expression of intestinal FXR protein was markedly increased. Oral administration of CDCA (90, 180 mg·kg-1·d-1, for 3 weeks) dose-dependently decreased the expression and function of intestinal PepT1 in rats. In conclusion, diabetes impairs the expression and function of intestinal PepT1 partly via CDCA-mediated FXR activation.

Physiologically based pharmacokinetic-pharmacodynamic modeling for prediction of vonoprazan pharmacokinetics and its inhibition on gastric acid secretion following intravenous/oral administration to rats, dogs and humans.

Vonoprazan is characterized as having a long-lasting antisecretory effect on gastric acid. In this study we developed a physiologically based pharmacokinetic (PBPK)-pharmacodynamic (PD) model linking to stomach to simultaneously predict vonoprazan pharmacokinetics and its antisecretory effects following administration to rats, dogs, and humans based on in vitro parameters. The vonoprazan disposition in the stomach was illustrated using a limited-membrane model. In vitro metabolic and transport parameters were derived from hepatic microsomes and Caco-2 cells, respectively. We found the most predicted plasma concentrations and pharmacokinetic parameters of vonoprazan in rats, dogs and humans were within twofold errors of the observed data. Free vonoprazan concentrations (fu × C2) in the stomach were simulated and linked to the antisecretory effects of the drug (I) (increases in pH or acid output) using the fomula dI/dt = k × fu × C2 × (Imax - I) - kd × I. The vonoprazan dissociation rate constant kd (0.00246 min-1) and inhibition index KI (35 nM) for H+/K+-ATPase were obtained from literatures. The vonoprazan-H+/K+-ATPase binding rate constant k was 0.07028 min-1· µM-1 using ratio of kd to KI. The predicted antisecretory effects were consistent with the observations following intravenous administration to rats (0.7 and 1.0 mg/kg), oral administration to dogs (0.3 and 1.0 mg/kg) and oral single dose or multidose to humans (20, 30, and 40 mg). Simulations showed that vonoprazan concentrations in stomach were 1000-fold higher than those in the plasma at 24 h following administration to human. Vonoprazan pharmacokinetics and its antisecretory effects may be predicted from in vitro data using the PBPK-PD model of the stomach. These findings may highlight 24-h antisecretory effects of vonoprazan in humans following single-dose or the sustained inhibition throughout each 24-h dosing interval during multidose administration.

Microarray expression profiles analysis revealed lncRNA OXCT1-AS1 promoted bladder cancer cell aggressiveness via miR-455-5p/JAK1 signaling.

Bladder cancer (BCa) is one of the most prevalent cancers of the urinary system worldwide. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) perform a vital function in the pathogenesis and progression of BCa. In the current study, we identified a novel lncRNA OXCT1-AS1 and investigated its role and potential mechanisms in BCa. The microarray results showed the expression of lncRNAs, microRNAs, and messenger RNAs between BCa primary tumor tissues and metastatic lymph nodes were significantly different. The quantitative polymerase chain reaction verification was performed to ensure the reliability of the screening results. The Cell Counting Kit 8 and transwell assay were used to assess the tumor cell proliferation and invasion abilities in vitro, respectively. The dual-luciferase activity assay was performed to investigate the potential mechanism of competing endogenous RNA network. lncRNA OXCT1-AS1, which elevated in metastasis lymph node, was significantly upregulated in BCa cell lines compared with SVHUC-1. We demonstrated OXCT1-AS1 inhibited miR-455-5p to decrease its binding to the JAK1 3'-untranslated region, which could upregulate the expression of JAK1 at the protein level, thus promoting BCa proliferation and invasion. Therefore, lncRNA OXCT1-AS1 could act as a potential biomarker and therapeutic target for patients with BCa.

PTEN improve renal fibrosis in vitro and in vivo through inhibiting FAK/AKT signaling pathway.

Renal fibrosis, the ultimate common pathway of progressive nephropathy, is characterized by excess accumulation and deposition of extracellular matrix (ECM) within the renal interstitium and glomeruli, finally resulting in end-stage kidney failure. TGFß1 is not only abnormally increased during fibrosis but also involved in ECM induction and accumulation. Based on the bioinformative analyses, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and focal adhesion kinase (FAK) signaling pathway might be involved in TGFß1 functions on renal fibrosis development. In the present study, fibrosis was induced in HK-2 cells using TGFß1 and PTEN expression was significantly suppressed by 24 or 48 hours TGFß1 treatment. PTEN overexpression in HK-2 cells improved TGFß1-induced fibrosis within α-SMA and E-cadherin. According to the KEGG signaling pathway annotation analyses on microarray profiles (GSE23338 and GSE20247) and immunoblotting validation, FAK signaling might be involved in PTEN functions in TGFß1-induced fibrosis. PTEN overexpression significantly inhibited TGFß1- or unilateral ureteral obstruction (UUO)-induced FAK signaling pathway activation both in vitro and in vivo; more importantly, PTEN silence enhanced TGFß1- or UUO-induced fibrosis, while FAK inhibitor PF567721 significantly reversed the effects of PTEN silence, indicating that PTEN exerted its effects on TGFß1- and UUO-induced fibrotic development in vitro and in vivo via inhibiting FAK signaling pathway. In summary, these findings indicate that PTEN could improve cellular fibrotic changes and renal fibrosis via inhibiting FAK/AKT signaling pathway. Restoring PTEN expression to target FAK/AKT signaling pathway might be a potent strategy for renal fibrosis treatment.

ISYNA1 is overexpressed in bladder carcinoma and regulates cell proliferation and apoptosis.

BACKGROUND: Bladder cancer (BCa) is one of the most common urological malignancies. While Inositol-3-phosphate synthase 1 (ISYNA1) expression and function were largely unknown in BCa. We aimed to study the expression and role of ISYNA1 in bladder cancer and investigate its potential mechanisms via ingenuity pathway analysis (IPA). METHODS: ISYNA1 expression was quantified by qRT-PCR in bladder cancer cell lines as well as normal urothelial cell line. Knocking down ISYNA1 gene in BCa T24 cells was achieved by shRNA lentivirus transfection. MTT and Celigo assay were used to assess cell proliferation. Flow cytometry was applied to test cell cycle and apoptosis. In addition, IPA was performed using PrimeView™ Human Gene Expression Array. Imunohistochemistry (IHC) was performed in BCa patient tissue microarray to verify the association between ISYNA1 expression and patients' clinicopathological features. RESULTS: ISYNA1 was significantly upregulated in BCa samples vs. para-tumor tissues. Higher expression were significantly associated with tumor T stage and lymph node metastasis of bladder cancer patients. Similarly, it was elevated in BCa cell lines (5637 and T24) compared with SVHUC cells. Knocking down ISYNA1 significantly decreased proliferation, induced apoptosis and cell cycle arrest in T24 cells. Furthermore, IPA indicated that ISYNA1 was an important regulatory factors and related networks were involved in multiple functional processes. CONCLUSION: Taken together, current study suggest ISYNA1 promotes proliferation and inhibit apoptosis in bladder cancer cells, and its expression correlated with BCa patients' clinicopathological features. Thus, ISYNA1 may serve as a potential biomarker and therapeutic target for BCa patients.

Tamsulosin as a Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Tamsulosin is widely administered as a medical expulsive therapy to facilitate stone passage in patients with ureteral calculi. Recently several large, multicenter, randomized controlled trials revealed conflicting results, which led to considerable uncertainty about the efficacy of tamsulosin in the management of ureteral stones. The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of tamsulosin in the management of ureteral stones. MATERIALS AND METHODS: We searched MEDLINE®, Embase®, Web of Knowledge, Google Scholar™ and the Cochrane Central Search Library databases up to June 2018. Two reviewers independently evaluated eligible randomized controlled trials of the efficacy of tamsulosin to treat ureteral stones. Study quality was assessed with the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. Subgroup analyses were performed to explore heterogeneity. RESULTS: Included in study were 56 randomized controlled trials in a total of 9,395 patients. The observed treatment effect indicated that tamsulosin was associated with a higher stone expulsion rate (RR 1.44, 95% CI 1.35-1.55, p <0.01), a shorter stone expulsion time (weighted mean difference -0.73, 95% CI -1.00--0.45, p <0.01), a lesser incidence of ureteral colic (weighted mean difference -0.81, 95% CI -1.24--0.39, p <0.01) and fewer incidences of requiring subsequent intervention (RR 0.68, 95% CI 0.50-0.93, p = 0.017). Treatment with tamsulosin did not differ from a control group in the overall incidence of side effects (RR 1.14, 95% CI 0.86-1.51, p = 0.36). On subgroup analysis we observed a significant benefit in the stone expulsion rate for tamsulosin among patients with stones greater than 5 mm (RR 1.44, 95% CI 1.22-1.68, p <0.01) but no effect for stones 5 mm or less (RR 1.08, 95% CI 0.99-1.68, p <0.01). CONCLUSIONS: Our current meta-analysis results indicate that tamsulosin is effective and relatively safe in patients with ureteral stone as a medical expulsive therapy to facilitate stone passage. It is suggested to administer it selectively in patients with 5 to 10 mm ureteral stones.

LncRNA-MALAT1 mediates cisplatin resistance via miR-101-3p/VEGF-C pathway in bladder cancer.

Cisplatin (CDDP)-based chemotherapy is a standard strategy for the clinical treatment of patients with bladder cancer (BC). However, the anti-tumor efficacy of cisplatin is affected by multiple chemoresistance with complex molecular mechanisms. Recent evidence highlights the crucial regulatory roles of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the progression of cancers and development of drug resistance. However, the roles and underlying molecular mechanisms of MALAT1 in cisplatin resistance of the BC cells remain largely unclear. In this study, we firstly demonstrated that MALAT1 expression was up-regulated in the BC tissues compared to the normal adjacent tissues and elevated in the cancer cells compared to the epithelial immortalized cells. Secondly, we found that suppression of MALAT1 enhanced the chemotherapeutic drug sensitivity and inhibited the cisplatin resistance of the BC cells. Thirdly, we showed that MALAT1 affected the cisplatin resistance of the BC cells via regulating the miR-101-3p/VEGF-C pathway. In summary, this study demonstrates that MALAT1, miR-101-3p and VEGF-C form a regulatory axis to affect the chemo-resistance of BC cells to CDDP, and provides novel potential targets for treatment of BC.

I2-catalyzed synthesis of 3-aminopyrrole with homopropargylic amines and nitrosoarenes.

The synthesis of 3-aminopyrrole using the amination reagent nitrosoarenes and homopropargylic amines catalyzed by I2 through cyclization and amination has been developed. This protocol features excellent functional group tolerance and mild reaction conditions, yielding 3-aminopyrroles in moderate to good yields without a metal catalyst. This method realizes the construction and amination of the 3-aminopyrroles in which nitrosoarenes serve as the amine source and oxidant.

Physicochemical characterization and cosmetic application of kelp blanching water polysaccharides.

Seaweeds account for half of global mariculture and have become a key player in bio-based industries. Seaweed process typically starts with hot water blanching that helps reduce postharvest quality deterioration but also generates large amounts of hydrothermal waste. This study aims to explore the feasibility of isolating water-soluble biopolymers from seaweed hydrothermal waste and their potential applications. Using Saccharina japonica (formerly Laminaria japonica) blanching water as example, 2.9 g/L of polymeric substances were efficiently isolated by ultrafiltration, implying biopolymer coproduction potential of ~5.8 kt from blanching wastewater of current kelp industry. Physicochemical characterizations revealed polysaccharidic nature of the biopolymers, with high contents of fucose, uronic acids and sulfate, showing distinct but also overlapping structural features with hot water-extracted kelp polysaccharides. The main fraction of the blanching water polymers after anion exchange chromatography was acidic polysaccharide, the major backbone residues of which were (1-4) linked mannopyranose, (1-4) linked gulopyranose and (1-2) linked fucopyranose while the branched residues were primarily 1,3,4-, 1,2,4- and 1,4,6-linked hexoses but also 1,3,4-fucopyranose. Furthermore, the polysaccharides were found to have a good compatibility in cosmetic creams with added cohesiveness and freshness, demonstrating the application potential of such natural biopolymers from currently underexplored seaweed blanching water.

Molecular vasculogenic mimicry-Related signatures predict clinical outcomes and therapeutic responses in bladder cancer: Results from real-world cohorts.

Bladder cancer (BLCA) is a heterogeneous disease, and there are many classical molecular subtypes that reflect tumor immune microenvironment (TME) heterogeneity but their clinical utility is limited and correct individual treatment and prognosis cannot be predicted based on them. To find reliable and effective biomarkers and tools for predicting patients' clinical responses to several therapies, we developed a new systemic indicator of molecular vasculogenic mimicry (VM)-related genes mediated by molecular subtypes based on the Xiangya cohort and additional external BLCA cohorts using a random forest algorithm. A correlation was then done between the VM_Score and classical molecular subtypes, clinical outcomes, immunophenotypes, and treatment options for BLCA. With the VM_Score, it is possible to predict classical molecular subtypes, immunophenotypes, prognosis, and therapeutic potential of BLCA with high accuracy. The VM_Scores of high levels indicate a more anticancer immune response but a worse prognosis due to a more basal and inflammatory phenotype. The VM_Score was also found associated with low sensitivity to antiangiogenic and targeted therapies targeting the FGFR3, ß-catenin, and PPAR-γ pathways but with high sensitivity to cancer immunotherapy, neoadjuvant chemotherapy, and radiotherapy. A number of aspects of BLCA biology were reflected in the VM_Score, providing new insights into precision medicine. Additionally, the VM_Score may be used as an indicator of pan-cancer immunotherapy response and prognosis.